A5063190899- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Signaling Pathways in Disease
- Chemical Synthesis and Analysis
- Enzyme function and inhibition
- Synthesis and Catalytic Reactions
- Histone Deacetylase Inhibitors Research
- Cell Adhesion Molecules Research
- HER2/EGFR in Cancer Research
- Sulfur-Based Synthesis Techniques
- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Synthesis and Biological Evaluation
- Ubiquitin and proteasome pathways
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Nanoparticle-Based Drug Delivery
- Ferrocene Chemistry and Applications
- Computational Drug Discovery Methods
- Chemical Reactions and Mechanisms
- Protein Hydrolysis and Bioactive Peptides
- S100 Proteins and Annexins
- Inflammatory mediators and NSAID effects
- Blood Coagulation and Thrombosis Mechanisms
- Phenothiazines and Benzothiazines Synthesis and Activities
University of Pisa
2016-2025
Temple University
2009-2016
University of Macau
2016
Instituto Superior Técnico
2009
University of Florence
2007-2008
Angiotensin II (AngII) has been strongly implicated in hypertension and its complications. Evidence suggests the mechanisms by which AngII elevates blood pressure enhances cardiovascular remodeling damage may be distinct. However, signal transduction cascade specifically initiates remodeling, such as hypertrophy fibrosis, remains insufficiently understood. In vascular smooth muscle cells, a metalloproteinase ADAM17 mediates epidermal growth factor receptor transactivation, responsible for...
Matrix metalloproteinases (MMPs) have been shown to be involved in tumor-induced angiogenesis. In particular, MMP-2, MMP-9, and MMP-14 reported crucial for tumor angiogenesis the formation of metastasis, thus becoming attractive targets cancer therapy. Here, we report our optimization effort identify novel N-isopropoxy-arylsulfonamide hydroxamates with improved inhibitory activity toward respect previously discovered compound 1. A new series was designed, synthesized, tested their...
Sulfonamides and coumarins incorporating arylsulfonylureido tails were prepared assayed as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Some derivatives 3-pyridinesulfonamide arylsulfonylureoido fragments low nanomolar isoforms CA II XII (upregulated or overexpressed in glaucoma) showed effective vivo intraocular pressure lowering effects an animal model disease, which several times better compared to those antiglaucoma drug dorzolamide. By means X-ray crystallography...
Matrix metalloproteinase-12 (MMP-12) selective inhibitors could play a role in the treatment of lung inflammatory and cardiovascular diseases. In present study, previously reported 4-methoxybiphenylsulfonyl hydroxamate carboxylate based (1b 2b) were modified to enhance their selectivity for MMP-12. newly synthesized thioaryl derivatives, nature zinc binding group (ZBG) sulfur oxidation state changed. Biological assays carried out vitro on human MMPs with resulting compounds led...
Hodgkin lymphoma (HL) resistant to conventional therapies is increasing, making of interest the search for new schemes treatment. Members "A Disintegrin And Metalloproteases" (ADAMs) family, mainly ADAM10 or ADAM17, have been proposed as therapeutic targets in solid tumors and some ADAMs inhibitors shown exert antitumor effects. We previously described an overexpression HL, together with increased release NKG2D ligands (NKG2D-L) reduced activation effector T lymphocytes anti-lymphoma...
Abstract Matrix metalloproteinase‐12 (MMP‐12) can be considered an attractive target to study selective inhibitors useful in the development of new therapies for lung and cardiovascular diseases. In this study, a series arylsulfonamide carboxylates, with increased hydrophilicity resulting from conjugation β‐ N ‐acetyl‐ d ‐glucosamine moiety, were designed synthesized as MMP‐12 inhibitors. Their inhibitory activity was evaluated on human MMPs by using fluorimetric assay, crystallographic...
Carbonic anhydrases (CAs) are metalloenzymes responsible for the reversible hydration of carbon dioxide to bicarbonate, a fundamental reaction involved in various physiological and pathological processes. In last decades, CAs have been considered as important drug targets different pathologies such glaucoma, epilepsy cancer. The design potent selective inhibitors has an outstanding goal leading discovery new drugs. Among strategies developed date, carbohydrate-based CA (CAIs) emerged...
Human carbonic anhydrases (hCAs) are involved in many physiological processes including respiration, pH control, ion transport, bone resorption, and gastric fluid secretion. Recently, CA IX XII have been studied for their role cancer diseases, motivating the design of inhibitors these isoforms. Here, we used tail approach to a new series monoaryl (1a-i) bicyclic (1j-n) benzensulfonamide derivatives inhibitors. All synthesized compounds were investigated toward panel hCAs, most them exhibited...
Ovarian cancer is the 3rd most common gynaecological malignancy worldwide, with a 5‐year survival rate of < 30% in presence metastasis. Metastatic progression characterised by extensive remodelling extracellular matrix, primarily mediated secreted proteases, including members ‘a disintegrin and metalloprotease thrombospondin motif’ (ADAMTS) family. In particular, ADAMTS5 has been reported to be upregulated ovarian malignant tumours compared borderline benign lesions, suggesting it might...
Matrix metalloproteinase-13 (MMP-13) is a key enzyme implicated in the degradation of extracellular matrix osteoarthritis (OA). For this reason, MMP-13 synthetic inhibitors are being sought as potential therapeutic agents to prevent cartilage and halt progression OA. Herein, we report synthesis vitro evaluation new series selective possessing an arylsulfonamidic scaffold. Among these inhibitors, very promising compound was discovered exhibiting nanomolar activity for highly compared MMP-1,...
Overexpression of macrophage elastase (MMP-12), a member the matrix metalloproteinases family, can be linked to tissue remodeling and degradation in some inflammatory processes, such as chronic obstructive pulmonary disease (COPD), emphysema, rheumatoid arthritis (RA), atherosclerosis. On this basis, MMP-12 considered an attractive target for studying selective inhibitors that are useful development new therapies COPD other diseases. We report herein design, synthesis, vitro evaluation...
New 1,1'-biphenylsulfonamides were synthesized and evaluated as inhibitors of the ubiquitous human carbonic anhydrase isoforms I, II, IX, XII, XIV using acetazolamide (AAZ) reference compound. The sulfonamides 1-21 inhibited all isoforms, with Ki values in nanomolar range concentration, superior to AAZ against them. X-ray crystallography molecular modeling studies on adducts that compound 20, most potent hCA inhibitor series (Ki = 0.26 nM), formed five hCAs, provided insight into...
Shedding of ADAM10 substrates, like TNFα, MICA or CD30, is reported to affect both anti-tumor immune response and antibody-drug-conjugate (ADC)-based immunotherapy. Soluble forms these molecules can be carried spread in the microenvironment by exosomes released tumor cells. We new inhibitors able prevent shedding Hodgkin lymphoma (HL), leading recognition HL cells cytotoxic lymphocytes. In this paper, we show that mature bioactive form exosome-like vesicles (ExoV) lymph node mesenchymal...